NEWTON, Mass.–(BUSINESS WIRE)–Siamab Therapeutics, Inc., a biopharmaceutical company developing novel
cancer immunotherapies, today announced the publication of new
preclinical data describing its novel ST1 antibodies targeting, with
high affinity and specificity, the Sialyl-Thomasen-nouveau antigen
(STn), a tumor-associated carbohydrate antigen (TACA). As antibody drug
conjugates (ADCs), these selective anti-STn antibodies possess potent
anti-tumor activity in in vitro and in vivo preclinical
cancer models. The paper, titled “Novel
anti-Sialyl-Tn monoclonal antibodies and antibody-drug conjugates
demonstrate tumor specificity and anti-tumor activity,” was
published online in the journal mAbs and will be available in the
May/June issue.

Siamab uses its proprietary technology platform to discover and develop
monoclonal antibody (mAb) therapeutics that bind to TACAs, a new class
of cancer-specific targets. ST1, the Company’s lead program, is in late
stage preclinical development and is expected to enter human clinical
trials in 2018.

“The paper describes the promise of our platform to unlock this exciting
class of cancer targets and highlights our unique approach to develop
highly specific anti-TACA therapeutic antibodies and antibody drug
conjugates that have the potential to not only eradicate cancer cells,
but also re-engage the immune system and overcome chemo-resistance,”
said Jeff Behrens, president and chief executive officer of Siamab
Therapeutics. “We are encouraged by the efficacy and safety findings for
ST1 in breast and colorectal cancer models, which add to our ovarian
cancer data presented last year at AACR and show we can have a
significant effect in vivo across a range of indications. We
continue to advance our ST1 program and plan to launch our first Phase 1
clinical trial for this program next year.”

TACAs, resulting from abnormal glycosylation, have been implicated in an
array of human diseases and are a common feature of cancer cells. They
are present in the majority of solid tumors including ovarian,
pancreatic, prostate, colon, gastric, and breast, and are exploited by
tumor cells to suppress innate immune function, enable tissue invasion
and metastasis, resist chemotherapy, and promote a stem-cell phenotype.

Siamab has identified novel antibodies that specifically target the STn
antigen with high affinity, and bind to STn independent of its carrier
protein. This discovery may lead to the identification of a wider array
of cancer-specific, abnormally sialylated proteins. The targeted
epitopes are glycan-specific and are present on multiple glycosylated
proteins on cancer cells. STn is expressed in numerous human
adenocarcinomas, including ovarian, pancreatic, prostate, colon,
gastric, and breast cancers. A STn-specific ADC offers significant
therapeutic potential.

ADCs utilize antibodies as targeting tools for delivering potent
cytotoxic payloads specifically to cancer cells. ADCs enable dosing of
highly cytotoxic chemotherapeutics at safe, therapeutic concentrations
by delivering the chemotherapeutic directly to the tumor. ADCs also have
been reported to stimulate immune system responses. To enable patient
selection, Siamab is also developing a companion diagnostic to identify
patients most likely to benefit from therapy.

The paper describes the power of Siamab’s technology platform to access
this new class of cancer targets and highlights the Company’s novel
approach to developing mAb therapeutics that target STn with
demonstrated high affinity, specificity and anti-tumor activity in
vitro and in vivo. Siamab scientists and collaborators
generated a panel of murine monoclonal anti-STn therapeutic antibodies
and characterized their binding specificity and efficacy in in vitro
and in vivo murine cancer models. The manuscript explains the
capabilities of Siamab’s glycan array to enable the screening and
development of highly specific antibodies, and illustrates how Siamab’s
internally generated anti-STn mAb selectively binds to STn, but not to
related structures. The scientists and collaborators used a subset of
these antibodies to generate ADCs consisting of anti-STn mAbs,
conjugated to monomethyl auristatin E (MMAE). The findings show that
these ADCs demonstrate in vitro efficacy in STn-expressing cell
lines and significant tumor growth inhibition in vivo in
STn-expressing tumor xenografts—both human breast and colon cancer
models—with no evidence of overt toxicity. In the subcutaneous human
breast cancer xenograft model, Siamab’s anti-STn ADCs generated a
dramatic reduction in tumor volume to 3.6% and 3.0%, respectively (both
p<0.001), and sustained tumor inhibition for a period of nearly four
weeks post treatment.

“Targeted therapies that can reliably differentiate between normal and
malignant tumor cells represent an ideal profile for cancer treatment,”
said Bo Rueda, Ph.D., director of the Vincent Center for Reproductive
Biology, in the Department of Obstetrics and Gynecology at Massachusetts
General Hospital and senior author of the paper. “STn is expressed by
more than 80% of ovarian carcinomas and until now has been a very
challenging target to access. The preclinical findings are encouraging
as we continue to study anti-STn antibody drug conjugates.”

About Siamab Therapeutics, Inc.

Siamab Therapeutics, Inc. is a biopharmaceutical company developing
novel cancer immunotherapies targeting cancer-specific carbohydrate
antigens seen in multiple solid tumors. Siamab has developed a platform
that enables the rapid discovery and development of therapeutic
antibodies that bind with unprecedented specificity and affinity to this
novel class of carbohydrate antigens present on cancer cells called
tumor associated carbohydrate antigens (TACAs). TACAs are an exciting
cancer target class due to their cancer specificity, association with a
chemoresistant phenotype, and ability to suppress immune function in the
region of solid tumors. The Company’s lead program, ST1, targets
Sialyl-Tn (STn), a tumor specific antigen seen in multiple solid tumors
including ovarian, pancreatic, prostate and colon cancers. ST1 is in
preclinical studies for the treatment of solid tumors. Visit www.siamab.com
to learn more about the Company.